{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:56:57Z","timestamp":1764935817535,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T00:00:00Z","timestamp":1482969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["T32GM067553"],"award-info":[{"award-number":["T32GM067553"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["R01ES023195"],"award-info":[{"award-number":["R01ES023195"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Identifying the locations of transcription factor binding sites is critical for understanding how gene transcription is regulated across different cell types and conditions. Chromatin accessibility experiments such as DNaseI sequencing (DNase-seq) and Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) produce genome-wide data that include distinct \u2018footprint\u2019 patterns at binding sites. Nearly all existing computational methods to detect footprints from these data assume that footprint signals are highly homogeneous across footprint sites. Additionally, a comprehensive and systematic comparison of footprinting methods for specifically identifying which motif sites for a specific factor are bound has not been performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using DNase-seq data from the ENCODE project, we show that a large degree of previously uncharacterized site-to-site variability exists in footprint signal across motif sites for a transcription factor. To model this heterogeneity in the data, we introduce a novel, supervised learning footprinter called Detecting Footprints Containing Motifs (DeFCoM). We compare DeFCoM to nine existing methods using evaluation sets from four human cell-lines and eighteen transcription factors and show that DeFCoM outperforms current methods in determining bound and unbound motif sites. We also analyze the impact of several biological and technical factors on the quality of footprint predictions to highlight important considerations when conducting footprint analyses and assessing the performance of footprint prediction methods. Finally, we show that DeFCoM can detect footprints using ATAC-seq data with similar accuracy as when using DNase-seq data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>Python code available at https:\/\/bitbucket.org\/bryancquach\/defcom<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btw740","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T04:06:05Z","timestamp":1479873965000},"page":"956-963","source":"Crossref","is-referenced-by-count":36,"title":["DeFCoM: analysis and modeling of transcription factor binding sites using a motif-centric genomic footprinter"],"prefix":"10.1093","volume":"33","author":[{"given":"Bryan","family":"Quach","sequence":"first","affiliation":[{"name":"Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Genetics, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Biology, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrence S","family":"Furey","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Biology, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,29]]},"reference":[{"key":"2023020205003114100_btw740-B1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1145\/130385.130401","volume-title":"Proceedings of the 5th Annual ACM Workshop on Computational Learning Theory","author":"Boser","year":"1992"},{"key":"2023020205003114100_btw740-B2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cell.2007.12.014","article-title":"High-resolution mapping and characterization of open chromatin across the genome","volume":"132","author":"Boyle","year":"2008","journal-title":"Cell"},{"key":"2023020205003114100_btw740-B3","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1093\/bioinformatics\/btn480","article-title":"F-Seq: a feature density estimator for high-throughput sequence tags","volume":"24","author":"Boyle","year":"2008","journal-title":"Bioinformatics"},{"key":"2023020205003114100_btw740-B4","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1101\/gr.112656.110","article-title":"High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells","volume":"21","author":"Boyle","year":"2011","journal-title":"Genome Res"},{"key":"2023020205003114100_btw740-B5","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nmeth.2688","article-title":"Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position","volume":"10","author":"Buenrostro","year":"2013","journal-title":"Nat. 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